Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of bovine serum albumin (BSA), rat serum albumin or rat plasma with medium conditioned by endotoxin stimulated rat peritoneal macrophages produced an activity that released histamine from isolated rat serosal mast cells. The amount of histamine-releasing activity (HRA) produced increased with the length of the incubation period, with the concentration of albumin, with the number of macrophages stimulated, and with the duration of exposure of the macrophages to endotoxin. Moreover, the formation of the HRA showed a dependency on the pH of the incubation medium with an optimum at pH 4.5. Boiling the medium conditioned by stimulated macrophages before its incubation with albumin or including the acid protease inhibitor, pepstatin with the conditioned medium prevented the formation of HRA. The generation of HRA was not inhibited by pretreatment of the macrophages with the inhibitor of protein synthesis, cycloheximide. Media from macrophages not stimulated with endotoxin failed to generate HRA. Histamine release from mast cells in response to the HRA was inhibited by pretreatment of the cells with antimycin A and deoxyglucose or by preincubation in Ca-free Locke's solution containing a calcium chelating agent. When injected intradermally into anesthetized Evan's Blue treated rats, the generated HRA produced a change in vascular permeability that was prevented by the H1 antagonist, diphenhydramine. Treatment of the HRA with carboxypeptidase A reduced its ability to stimulate histamine release from mast cells. Histamine-Releasing Peptide (HRP), a neurotensin-related octapeptide, shown previously by us to be formed by the action of cathepsin D or pepsin on albumin, was identified by radioimmunoassay in acid:acetone extracts of the histamine-releasing activity. It is concluded that the formation of HRA is due to the actions of enzymes released from macrophages acting on albumin. It is suggested that such histamine-releasing activity could be formed during the later stages of the inflammatory response and that HRP is one of the peptides present.
 ...
PMID:Formation of histamine-releasing activity from albumin by medium conditioned by endotoxin-stimulated rat peritoneal macrophages. 138 Jul 64

We investigated the cellular and subcellular distribution of surfactant protein D (SP-D) by immunogold labeling in lungs of adult rats that had been given bovine serum albumin coupled to 5-nm gold (BSAG) for 2 hr to visualize the endocytotic pathway. Specific gold labeling for SP-D was found in alveolar Type II cells, Clara cells, and alveolar macrophages. In Type II cells abundant labeling was observed in the endoplasmic reticulum, whereas the Golgi complex and multivesicular bodies were labeled to a limited extent only. Lamellar bodies did not seem to contain SP-D. Gold labeling in alveolar macrophages was restricted to structures containing endocytosed BSAG. In Clara cells labeling was found in the endoplasmic reticulum, the Golgi complex, and was most prominent in granules present in the apical domain of the cell. Double labeling experiments with anti-surfactant protein A (SP-A) showed that both SP-A and SP-D were present in the same granules. However, SP-A was distributed throughout the granule contents, whereas SP-D was confined to the periphery of the granule. The Clara cell granules are considered secretory granules and not lysosomes, because they were not labeled for the lysosomal markers cathepsin D and LGP120, and they did not contain endocytosed BSAG.
 ...
PMID:Immunocytochemical localization of surfactant protein D (SP-D) in type II cells, Clara cells, and alveolar macrophages of rat lung. 152 77

Subcellular fractionation of human monocyte-macrophages (HMM) yielded a fraction rich in endosomes, lysosomes, and mitochondria. This pellet was further fractionated in a metrizamide gradient and the subcellular organelles were distributed among seven distinct bands. All of the bands contained lysosomal enzymes in similar amounts. However one band, poor in mitochondria, was markedly enriched in cathepsin D and cholesteryl ester hydrolase activities. A number of different ligands (low density lipoproteins (LDL), malondialdehyde-altered LDL, beta-migrating very low density lipoprotein, high density lipoprotein, reductively methylated LDL, mannose-bovine serum albumin, and transferrin) were presented to HMM at a concentration of 20 micrograms/ml at 4 degrees C. Three minutes after warming the cells at 37 degrees C all ligands except two were found predominantly in the cathepsin D- and cholesteryl ester hydrolase-rich fraction. Unlike the other ligands, LDL had distributed to other more dense fractions and reductively methylated LDL was found mainly in less dense fractions. At a lower concentration, 2 micrograms/ml, the distribution of LDL was identical to the other ligands. In vitro incubation of the fractions obtained from the gradient suggested that cathepsin D was largely responsible for the hydrolysis of the lipoproteins. We conclude that studies of LDL metabolism in HMM must take into account the different processing of this ligand at commonly used concentrations.
 ...
PMID:Processing of lipoproteins in human monocyte-macrophages. 214 42

Treatment of human serum albumin with a proteolytic enzyme such as pepsin, alpha-chymotrypsin, cathepsin D or trypsin generated histamine releasing peptides. A low-molecular weight peptide (P-1) responsible for releasing histamine was isolated from peptic digests of human serum albumin by affinity chromatography on heparin-Ultrogel and reversed-phase high performance liquid chromatography. The amino acid sequence of the P-1 was estimated to be V-R-Y-T-K-K-V-P-Q-V-S-T-P-T-L by Edman degradation. The sequence determined appears to correspond to residues 409-423 of human serum albumin. Peptide P-1 produced dose-related histamine release from isolated rat mast cells in the concentration range of 1-50 microM. The intradermal injection of the P-1 (0.5 micrograms) increased capillary permeability in rats. This response was blocked by the antihistamine diphenhydramine.
 ...
PMID:Histamine release induced by proteolytic digests of human serum albumin: isolation and structure of an active peptide from pepsin treatment. 247 58

The acid proteases, pepsin, rennin and cathepsin D, were shown to generate mast cell histamine releasing peptides (HRP) when incubated with the albumin fraction of mammalian plasmas. Significant histamine release was observed using less than 1 microliter equivalent of pepsin-treated plasma. Histamine release was rapid, dependent on calcium and energy, and accompanied by degranulation. The major HRP present in pepsin-treated human and canine plasma was identified as H-Ile-Ala-Arg-Arg-His-Pro-Tyr-Phe-OH whereas that from rat plasma had valine substituted for isoleucine. Cathepsin D-treated BSA gave rise to the human octapeptide (above) as well as to an extended decapeptide with H-Tyr-Glu- at the N-terminus. These peptides were apparently derived from one region of serum albumin, residues 139 to 149 of the human, canine, or bovine sequence. We hypothesize that cathepsin D, released from leukocyte lysosomes, might generate HRP during the delayed phase of an inflammatory response.
 ...
PMID:Structures of histamine-releasing peptides formed by the action of acid proteases on mammalian albumin(s). 247 9

Self-quenched fluorogenic substrates for proteolytic enzymes have been prepared by alkylation of thiol groups in reduced bovine serum albumin with iodoacetamidofluorescein or iodoacetamidoeosin. Substrates immobilized by adsorption onto nitrocellulose membranes or by incorporation into agarose gel slabs are suitable for fluorescence zymography after electrophoretic separation of catalytically active proteases, including cathepsin D.
 ...
PMID:Self-quenched fluorogenic protein substrates for the detection of cathepsin D and other protease activities. 266 7

Three peaks of proteinases were observed with hemoglobin, bovine serum albumin and casein as substrates at the pH of 3.5, 6.5 and 8.5, in prenatal human cerebral cortex. Cathepsin D (EC 3.4.23.5) was the most prominent, with hemoglobin as the preferred substrate. The enzyme was partially purified by Concanavalin A - Sepharose affinity chromatography and the nature of the active site was assessed with proteinase inhibitors. Inhibitor studies showed that similar to pepstatin A, benzethonium chloride was also strongly inhibitory to the enzyme. The distribution of cathepsin D, a neuronal marker, and 2',3'-cyclic nucleotide 3'-phosphohydrolase (EC 3.1.4.37), a oligodendroglial marker in foetal brain regions with increasing gestation revealed that neurogenesis and gliogenesis occur concomitantly from earlier periods of gestation. Glial marker acquisition was particularly high in medulla and in spinal cord between 20 and 25 weeks of gestation.
 ...
PMID:Cathepsin D and 2',3'-cyclic nucleotide 3'-phosphohydrolase in developing human foetal brain. 321 74

Hemolysates of human erythrocytes contain a highly specific insulin- and glucagon-degrading activity which is comparable to the so-called insulin- and glucagon-degrading proteinase (IGP, EC 3.4.23.5) found in other tissues. Glucagon degradation is inhibited by its cleavage products. Insulin, proinsulin and also cleavage products of insulin are effective inhibitors of glucagon degradation. The isolated insulin A- and B-chains are also capable of inhibiting the splitting of glucagon, but a higher concentrations. On the other hand, glucagon influences insulin degradation. Naturally occurring substances within commercially available human serum albumin have remarkable inhibitory effects on the glucagon degradation.
 ...
PMID:Glucagon- and insulin degradation by hemolysate of human erythrocytes. 332 71

An erythrocyte membrane-associated cathepsin D-like acid proteinase, termed "EMAP," was purified to homogeneity from freshly collected rat blood in a yield of 60-65%. The molecular weight of the enzyme was determined to be 80,000-82,000 by Sephadex G-100 gel filtration. The enzyme was inhibited strongly by pepstatin and partially by HgCl2, Pb(NO3)2, and iodoacetic acid. The preferred substrate for the enzyme was hemoglobin. The enzyme also hydrolyzed serum albumin and casein, but to lesser extents, with an optimum pH of 3.5-4.0. However, it could not hydrolyze leucyl-2-naphthylamide, benzyloxycarbonyl-Phe-Arg-4-methyl-7-coumarylamide or other synthetic substrates at pH values ranging from 3.5 to 9.5. The enzyme was very similar to human EMAP in a number of enzymatic properties, whereas it differed from rat cathepsin D in several respects, such as pH stability, molecular weight, isoelectric point, and chromatographic properties. Immunologically, the enzyme cross-reacted with the rabbit antibody prepared against human EMAP. The patterns of immunoelectrophoresis, immunoblotting, and immunoprecipitation of the enzyme were remarkably similar, if not identical, to those of human EMAP. In contrast, rat EMAP showed no reaction with the rabbit antibody raised to rat spleen cathepsin D. These results indicate that EMAP is a unique cathepsin D-like acid proteinase different from ordinary cathepsin D.
 ...
PMID:Isolation, and catalytic and immunochemical properties of cathepsin D-like acid proteinase from rat erythrocytes. 354 79

The proteolytic activity of bovine splenic cathepsin D was evaluated by using the digestion of tritiated hemoglobin. Acid-denatured human serum was an enhancer of cathepsin D activity. Concentrated serum sources showed decreased activity because of competition of serum albumin with tritiated hemoglobin for cathepsin D. The enhancing activity of serum did not separate with any isolated protein as assessed by Sephadex G-50-80 chromatography or protein electrophoresis. The extraction of serum with ethanol-ether and chloroform-methanol showed that the enhancing activity separated with the phospholipid fraction, which had 2.6 times as much activity as the total lipid fraction. The activity was stable to heat at 56 degrees C for 30 minutes and to freeze-thawing, and was not dependent on metal ions.
 ...
PMID:Effects of human serum on cathepsin D activity. 359 36


<< Previous 1 2 3 4 5 6 Next >>